RNA Splicing Mutation in an Aberrantly Rearranged Immunoglobulin λ I Gene

The mouse cell line MOPC 315 is an IgA (λ II)-producing myeloma. We have studied a derivative of MOPC 315 that secretes normal λ II chains but no heavy chain. This derivative, MOPC 315-26, was found to contain a rearranged λ I gene in addition to a rearranged λ II gene. The rearranged λ I gene was cloned into bacteriophage λ DNA and its structure was studied. The λ I gene was found to have arisen by an aberrant recombination event that resulted in a single base insertion at the site of V-J region joining. In addition, the gene contained numerous point mutations in the vicinity of the junction of the V and J regions. Two point mutations occurred in the donor splice sequence normally used for the removal of the intron between the J and C regions, suggesting that the RNA synthesized from the aberrantly rearranged λ I gene would be unable to undergo proper RNA splicing.